Biology Reference
In-Depth Information
migration, the c-Met receptor expressing precursors receive a constant SF/
HGF signal. The controlled spatial localization of SF/HGF expression
indicates that c-Met signalling is of importance during the migration process
(Dietrich et al., 1999; Scaal et al., 1999).
A genetic analysis in mice revealed the importance of the adaptor molecule
Gab1 for signal transduction of c-Met. Gab1-mutant mice display phenotypes
that closely resemble those present in c-Met or SF/HGF mutants. In
particular, the development of muscle groups that derive from migrating
progenitors is impaired; some of these muscles, like those present in the distal
limbs, are completely absent, whereas others like the flexor muscles in the
proximal forelimb are formed but are reduced in size. Delamination of muscle
progenitor cells from the dermomyotome occurs, but is strongly reduced in
e ciency. Compared with control mice, less cells leave the somites in Gab1
mutants, and the precursor stream headed towards the targets contains a
reduced number of cells (Sachs et al., 2000).
The homeobox gene Lbx1 is essential for correct target finding
of migrating muscle precursor cells
Lbx1 encodes a mammalian homeodomain factor that was discovered because
of its homology to the ladybird genes of Drosophila. During muscle
development, expression of Lbx1 is restricted to the migratory lineage
(Jagla et al., 1995). Lbx1 is induced prior to delamination, maintained during
migration and downregulated when the cells differentiate. This restricted
expression pattern implied a role of the gene in the migrating lineage.
Migratory muscle precursors form and delaminate from the dermomyo-
tome, but migrate in an abnormal manner in Lbx1 mutants (Scha¨ fer and
Braun, 1999; Brohmann et al., 2000; Gross et al., 2000). Most strongly
affected are those cells destined to move to the limbs. They fail to move
laterally towards the limbs and migrate ventrally instead. The misrouted cells
accumulate in the mesoderm of the ventral body wall, and their migratory
path is similar to that taken by cells that move towards the anlage of the
diaphragm. A few progenitors reach the proximo-ventral field of the forelimb,
but arrive delayed. As a consequence, most muscles in the hindlimbs and the
extensor muscles in the forelimbs are absent, while flexor muscles in the
forelimbs are reduced in size. Premature myogenic differentiation can interfere
with migration of hypaxial muscle precursor cells, but is not responsible for
the misrouting in Lbx1 mutants, since precursor cells are observed at aberrant
positions prior to their differentiation. Rather, migrating cells appear to be
unable to recognize or to interpret cues that direct them, implying a defective
guidance mechanism in the mutants. It was therefore suggested that Lbx1
Search WWH ::




Custom Search